Showing papers on "Angiotensin II published in 1974"
TL;DR: The changes in ventricular weight with the onset of hypertension and with its reversal or its prevention suggest that blood pressure might not be the sole factor contributing to cardiac hypertrophy in the spontaneously hypertensive rat and that the renin-angiotensin system might play a permissive role enhancing myocardialhypertrophy.
Abstract: Ventricular weight in spontaneously hypertensive rats (F26 generation, Okamoto-Aoki strain) was significantly higher (P < 0.001) than that in body weight-matched American Wistar and Kyoto-Wistar normotensive rats, not only among older groups of rats but also among younger groups that had not developed significant hypertension. Deoxyribonucleic acid (DNA) concentration in ventricular muscle was not different from normal in the youngest group (P < 0.4) but was significantly reduced in the older spontaneously hypertensive rats (P < 0.01). Plasma renin activity was significantly increased in younger spontaneously hypertensive rats before the development of established hypertension; moreover, ventricular weight and plasma renin activity were significantly correlated in younger rats (r = 0.788, P < 0.005 for all rats, r = 0.644, P < 0.01 for spontaneously hypertensive rats). Antihypertensive therapy with either α-methyldopa or hydralazine reduced blood pressure, especially in hypertensive rats; however, ventric...
472 citations
TL;DR: Sodium intake reciprocally influences vascular and adrenal responses to A II: salt restriction blunts the vascular response and potentiates the adrenal's, a physiologically important influence in view of aldosterone's role in sodium conservation.
Abstract: The adrenal glomerulosa cell and the renal vasculature respond to similar arterial angiotensin II (A II) levels We have assessed the effect of decreased sodium intake on their responses to A II in man Studies were performed in 42 normal subjects in balance on a daily intake of 100 meq potassium and either 200 or 10 meq sodium/day Renal blood flow was measured with 133Xe and arterial A II, renin and aldosterone concentrations by radioimmunoassay A II was infused intravenously (1, 3, or 10 ng/kg/min) for 40—60 min; 14 subjects received graded doses The A II level increased linearly with dose and plateaued within 3 min; blood pressure and renal vascular resistance showed a similar time-course Aldosterone rose within 10 and plateaued within 20 min Dose-response relationships were established between the rate of A II infusion and the adrenal, the renal vascular, and pressor responses Sodium restriction reduced the pressor (P < 001) and the renal vascular response (P < 001), but potentiated the adrenal response to A II (P < 001) An excellent correlation was found between the plasma A II and aldosterone levels, but the slope of their regression relationship on a high (y = 013x + 6) and low salt intake (y = 032x + 14) differed significantly (P < 00005) Thus, sodium intake reciprocally influences vascular and adrenal responses to A II: salt restriction blunts the vascular response and potentiates the adrenal's, a physiologically important influence in view of aldosterone's role in sodium conservation
340 citations
TL;DR: The role of the kidney in blood-pressure regulation was established by TIGERSTEDT and Bergman at the close of the 19th century as discussed by the authors, who produced hypertension in dogs by injecting a cr...
Abstract: TIGERSTEDT and Bergman established a role for the kidney in blood-pressure regulation at the close of the 19th century. In a classic experiment, they produced hypertension in dogs by injecting a cr...
278 citations
TL;DR: The presence of high affinity specific binding sites for angiotensin II in bovine and rat adrenal cortex and suggest a plasma membrane location for the angiotENSin II receptors are illustrated.
240 citations
TL;DR: The contrasting effects of sodium depletion on the aldosterone and the pressor dose-response curves favored sodium retention, consistent with an important role for the renin-angiotensin system in the control of ald testosterone secretion in man.
Abstract: The effect of sodium depletion on the dose-response relationships of angiotensin II to aldosterone and blood pressure was studied. Arterial plasma angiotensin II and aldosterone and arterial blood pressure were measured before and during the incremental infusion of angiotensin II into sodium-replete and sodium-deplete subjects. Sodium depletion caused a distinct steepening of the angiotensin Il-aldosterone dose-response curves in four of five subjects and a concurrent diminution in the pressor effect of angiotensin II. Administration of angiotensin II did not demonstrably alter the half-life of aldosterone. Sodium depletion did not change the plasma concentrations of sodium or potassium, but it was accompanied by a significant increase in plasma levels of 11-hydroxycorticosteroids and magnesium. The contrasting effects of sodium depletion on the aldosterone and the pressor dose-response curves favored sodium retention. These results are consistent with an important role for the renin-angiotensin system in the control of aldosterone secretion in man.
207 citations
TL;DR: Ninety-three per cent of nulliparous, normotensive young women who subsequently developed pregnancy-induced hypertension demonstrated an increase in diastolic blood pressure of at least 20 mm Hg when turned from the lateral recumbent to the supine position between the twenty-eighth and thirty-second weeks of gestation.
204 citations
TL;DR: There are several reasons for interest in the maternal hemodynamic adjustments that accompany pregnancy, and an understanding of these reversible changes and the mechanisms regulating them will lead to increased knowledge concerning the physiology of the circulation and its control.
189 citations
TL;DR: The La-method was able to show that the slow phase of a norepinephrine induced contraction is dependent on Ca2+ influx, and the large rapid initial phases of these three types of drug induced aortic contractions were dependent on a common intracellularCa2+ store which was rapidly exhausted in the presence of extracellular La3+.
Abstract: Using the “La-method” for measuring45Ca entry into smooth muscle cells we were able to show that the slow phase of a norepinephrine induced contraction is dependent on Ca2+ influx. Similarly Ca2+ influx was stimulated during the slow phase of angiotensin II and histamine induced contractions. The large rapid initial phases of these three types of drug induced aortic contractions were dependent on a common intracellular Ca2+ store which was rapidly exhausted in the presence of extracellular La3+.
188 citations
TL;DR: Patients who were comatose after head injuries were studied with serial determinations of regional cerebral blood flow, jugular PO2 tension, and intraventricular pressure to suggest a need for therapeutic maintenance of rich oxygenation, hyperventilation with moderate hypocapnia, and steady blood pressure.
Abstract: Twelve patients who were comatose after head injuries were studied with serial determinations of regional cerebral blood flow, jugular PO2 tension, and intraventricular pressure. These determinations began a few hours after the injury, and were followed throughout the clinical course. Diffuse derangement of cerebral vasomotor regulation is confirmed after severe head trauma, which may contribute to deterioration and poor prognosis, and which indicates a need for therapeutic maintenance of rich oxygenation, hyperventilation with moderate hypocapnia, and steady blood pressure. Continuous recording of IVP (eventually sensitized by fluid infusion or CO2 inhalation tests) may give an early indication of the subsequent clinical state and may suggest the need to submit the patients to further investigative and therapeutic procedures.
148 citations
TL;DR: Specific binding of angiotensin II at physiological plasma concentration to rat glomeruli and correlation of this binding withglomerular vasoreactivity suggest a physiological role for this hormone in regulation of glomerular filtration.
141 citations
TL;DR: It is proposed that the actions of the guanyl nucleotides are based on a conformational change at the receptor level that leads to a lower steady state binding of the hormone to its receptor and a rapid release of bound tracer angiotensin II.
TL;DR: Norepinephrine responsiveness and nore Pinephrine stores are normal, and there is suppression of RRA leading to decreased PRA and increased vascular reactivity to angiotensin II in the acutely diabetic alloxan-treated rat.
Abstract: The renin-angiotensin system and catecholamines were evaluated in short term alloxan diabetic rats which were either “severely diabetic” (polyuric with serum glucose > 450 mg. per 100 ml.) or “mildly diabetic” (normouric with serum glucose Blood volume as related to lean body mass was elevated in the severely diabetic rats thus suggesting one possible mechanism for the decrease in the renin-angiotensin system. These results suggest that (1) norepinephrine responsiveness and norepinephrine stores are normal, and (2) there is suppression of RRA leading to decreased PRA and increased vascular reactivity to angiotensin II in the acutely diabetic alloxan-treated rat. Further, these abnormalities appear to be related to the degree of diabetes as assessed by serum glucose and twenty-four hour urine volume.
Journal Article•
TL;DR: The results suggest that the principal determinant of pressor response to angiotensin II in pregnancy is arteriole response and not alterations in plasma volume or renin plasma levels.
TL;DR: Investigation of the possible participation of locally synthesised prostaglandins in the regulation of blood flow and vascular reactivity of the gravid uterus finds that the uterus synthesises prostag landins.
Abstract: IN late pregnancy, uterine blood flow (UBF) has increased by as much as thirty- to forty-fold1 and uterine vascular reactivity to vasoconstrictor hormones and adrenergic nerve stimulation has decreased2,3. For example, angiotensin II increases blood flow to the gravid uterus3,4, an uncommon response to this agent which is the most potent vasoconstrictor hormone5. Prostaglandins of the E series (PGE) have been reported to maintain some regional blood flows6,7 and to modulate the vasoconstrictor activity of angiotensin II and noradrenaline8,9. In view of the findings that the uterus synthesises prostaglandins10,11, we have investigated the possible participation of locally synthesised prostaglandins in the regulation of blood flow and vascular reactivity of the gravid uterus.
TL;DR: It is suggested that renin-binding protein may act as a carrier for the transport of renin to local tissue sites of uptake under some circumstances and thus alter the mode of expression of the ren in-angiotensin system in vivo to one of local angiotENSin generation and effect.
Abstract: Two interconvertible renins were isolated from extracts of the pig renal cortex at neutral pH and shown to be protein-bound (renin B, molecular weight 60,000) and free (renin A, molecular weight 40,000) forms of renin. The protein-bound form (renin B) gave a much more prolonged pressor response than did the free form (renin A) on direct bioassay in the rat; it could be converted to renin A by the action of various salts or by acidification below pH 3. The renin-binding protein associated with renin B was isolated by DEAE-cellulose column chromatography under special conditions of elution and appeared to be specific for renin. When pig kidneys were perfused in situ with Krebs-Ringer's solution, isoproterenol stimulation (1-8 µg/min) resulted in release of renin in the protein-bound form. It is suggested that renin-binding protein may act as a carrier for the transport of renin to local tissue sites of uptake under some circumstances and thus alter the mode of expression of the renin-angiotensin system in v...
TL;DR: Results indicate that angiotensin controls aldosterone release in the rat and that des-aspartyl-angiotens in II (that is, angiotENSin III) may be important in this sequence.
Abstract: The potential role of angiotensin II and its heptapeptide metabolite, des-aspartyl-angiotensin II, was studied in the conscious unanesthetized rat. Aldosterone release was induced by both peptides at physiologic doses (0.72 nanogram per minute). [I-Sarcosyl-8-alanyl]-angiotensin II (P-113 inhibited angiotensin II more effectively than des-aspartyl-angiotensin II (101 percent as compared to 82 percent). These results indicate that angiotensin controls aldosterone release in the rat and that des-aspartyl-angiotensin II (that is, angiotensin III) may be important in this sequence.
TL;DR: The observations indicate that the inhibitory effect of biologically active angiotensin, on basal and isoprenaline‐stimulated renin secretion, is functionally related to the contractor response by its dependence on calcium.
Abstract: 1 The effect of calcium on the inhibition of renin secretion by biologically active angiotensin was investigated in the isolated rat kidney perfused with Krebs-Ringer saline.
2 In the presence of calcium (3.7 mM), asp(NH2)′-angiotensin II suppressed both basal and isoprenaline-stimulated renin secretion. Renal perfusion pressure, which was increased by the infusion of angiotensin, returned to control levels when isoprenaline was added.
3 When the calcium concentration was reduced to 0.32 mM, the vasoconstriction produced by angiotensin was abolished although the inhibitory effect on renin secretion was still evident.
4 In the absence of calcium, angiotensin no longer suppressed basal renin secretion and a prompt increase in renin secretion occurred when isoprenaline was added.
5 The higher basal renin levels which were observed in calcium-free perfusions, suggest the existence of an intrarenal calcium-dependent mechanism that regulates basal renin secretion.
6 These observations indicate that the inhibitory effect of biologically active angiotensin, on basal and isoprenaline-stimulated renin secretion, is functionally related to the contractor response by its dependence on calcium. The recognition that the renin-producing cells are modified smooth muscle cells supports this association
TL;DR: A possible involvement of angiotensin as a rapid and direct facilitator of sodium intake (apart from a slow and indirect role through stimulation of aldosterone release) has not yet been reported and some evidence suggests that angiotensor may not play any significant role in regulating sodium intake in the rat.
Abstract: ANGIOTENSIN II induces short-latency water intake when infused intravascularly or injected into certain brain regions of mammals1,2. But conceptual difficulties arise if one asks why this should be so, and whether the data reflect real physiological actions. For example, angiotensin is a pressor hormone formed from kidney-based renin in response to challenge such as hypotension and hypovolaemia3–7. Water ingestion, in itself, is not an adaptive response to such challenges, since most ingested water is distributed intracellularly and will not relieve a vascular crisis. An adaptive response to hypotension or hypovolaemia would involve ingestion of an isotonic mix of fluids, since this would most rapidly and effectively increase vascular volume. In fact, hypovolaemia does result in an immediate increase in preference for isotonic saline over water and a delayed (6–10 h) acceptance of unpalatable hypertonic salt solutions8,9. But, a possible involvement of angiotensin as a rapid and direct facilitator of sodium intake (apart from a slow and indirect role through stimulation of aldosterone release) has not yet been reported and some evidence suggests that angiotensin may not play any significant role in regulating sodium intake in the rat10–12.
Journal Article•
TL;DR: Catecholamine-induced PG release thus appears to be mediated by alpha adrenergic receptor site stimulation, and this was confirmed by the finding that blockade was achieved with phenoxybenzamine but not propranolol.
Abstract: Epinephrine and norepinephrine caused vasoconstriction and prostaglandin (PG) release when administered to the isolated perfused rabbit kidney. Dopamine was only about 0.1% as potent as epinephrine as a PG releaser, and isoproterenol did not cause renal PG release. Catecholamine-induced PG release thus appears to be mediated by alpha adrenergic receptor site stimulation, and this was confirmed by the finding that blockade was achieved with phenoxybenzamine but not propranolol. Phenoxybenzarnine did not block PG release induced by angiotensin II, but indomethacin (PG synthesis inhibitor) blocked all PG release. Renal nerve stimulation caused the rabbit kidney to release PG, and this release was blocked by phenoxybenzamine or indomethacin. Paradoxically, tyramine did not cause PG release. Renal ischemia caused PG release which was blocked by indomethacin but was not blocked by phenoxybenzamine and/or propranolol.
TL;DR: The influence of treatment with progesterone and with 4 synthetic progestagens for 6 days on sodium balance and on different factors of the renin-aldosterone system was investigated in 20 young healthy men on a fixed sodium intake.
Abstract: The influence of treatment with progesterone and with 4 synthetic progestagens (megestrol-acetate, dydrogesterone, norethisterone-acetate, d-norgestrel) for 6 days on sodium balance and on different factors of the renin-aldosterone system was investigated in 20 young healthy men on a fixed sodium intake (83 mEq/day). 50 mg of progesterone im caused, as expected, natriuresis, an increase in plasma renin activity (PRA), plasma angiotensin II concentration (PAC) and aldosterone excretion (AER), while plasma renin substrate concentration (PRS) remained unchanged. Progesterone levels during treatment were somewhat lower than in the luteal phase of normal menstrual cycles in women. Megestrol-acetate (15 mg/day) did not influence sodium balance, but led to a slight increase in PRA and AER after 3 days of treatment. PAC and PRS remained unchanged. Dydrogesterone (30 mg/day) caused slight sodium retention after 3 days of treatment and a concomitant increase in PRA, PAC (upright posture) and AER, but PRS w...
TL;DR: The results suggest that an action of angiotensin II that is separate from its pressor activity is specifically required for a significant vasoconstrictor response to hypoxia in isolated rat lungs.
Abstract: In isolated blood-perfused rat lungs, brief periods of ventilation hypoxia (2% O2) produce pulmonary vasoconstriction. In isolated lungs perfused with a salt-albumin solution, hypoxia produces no pulmonary vasoconstrictor responses in most preparations and only minimal responses in others. Vasoactive agents including angiotensin II, phenylephrine, epinephrine, norepinephrine, bradykinin, histamine, serotonin, and methoxamine were added to the salt-albumin perfusate to determine which substance, if any, was necessary for a pulmonary vasoconstrictor response during hypoxia. The addition of angiotensin II (12-120 nM) to the perfusate during hypoxia resulted in marked pulmonary vasoconstriction in proportion to the amount of angiotensin II added (a maximal response to hypoxia occurred with 120 nM angiotensin II). None of the other agents had the same effect, nor was their vasoactivity dependent on angiotensin II. Angiotensin II augmented the hypoxic response in doses that are themselves subpressor; tachyphylaxis to the direct pressor activity of angiotensin II was not associated with attenuation of the hypoxic response. These results suggest that an action of angiotensin II that is separate from its pressor activity is specifically required for a significant vasoconstrictor response to hypoxia in isolated rat lungs.
TL;DR: Chronic ethanol ingestion in this animal model is associated with abnormalities of ventricular function without evident malnutrition, analogous to the preclinical malfunction described in the human alcoholic.
Abstract: In view of the variables that obscure the pathogenesis of cardiomyopathy, a study was undertaken in mongrel dogs fed ethanol as 36% of calories for up to 22 mo. Both the experimental and control groups maintained body weight, hematocrit, plasma vitamin, and protein levels. Left ventricular function was evaluated in the intact anesthetized dog using indicator dilution for end-diastolic and stroke volume determinations. During increased afterload with angiotensin, the ethanol group exhibited a larger rise of end-diastolic pressure (P<0.01), whereas end-diastolic and stroke volume responses were significantly less than in controls. Preload increments with saline elicited a significantly higher end-diastolic pressure rise in the ethanol group (P<0.01). No hypertrophy, inflammation, or fibrosis was present and it was postulated that the enhanced diastolic stiffness was related to accumulation of Alcian Blue-positive material in the ventricular interstitium. To evaluate myocardial lipid metabolism, [1-(14)C]oleic acid was infused systemically. Plasma specific activity and myocardial lipid uptake were similar in both groups. There was a significantly increased incorporation of label into triglyceride, associated with a reduced (14)CO(2) production, considered the basis for a twofold increment of triglyceride content. In addition, diminished incorporation of [(14)C]oleic acid into phospholipid was observed accompanied by morphologic abnormalities of cardiac cell membranes. Potassium loss and sodium gain, like the lipid alteration, was more prominent in the subendocardium. Thus, chronic ethanol ingestion in this animal model is associated with abnormalities of ventricular function without evident malnutrition, analogous to the preclinical malfunction described in the human alcoholic.
TL;DR: In this article, the authors found that renin and angiotensin II levels in foetal lambs were significantly higher in the presence of additional substrate than in their mothers.
Abstract: 1. Plasma renin (measured in the presence of additional substrate) was significantly higher (10.7 +/- 1.1 S.E. of mean ng/ml.hr) in foetal lambs of 111-144 days gestation age (full term 147 days) than in their mothers (1.5 +/- 0.2 ng/ml.hr S.E. of mean, P < 0.001) but plasma angiotensin II concentrations were in the same range (ewe 47.3 +/- 6.6 S.E. of mean, foetus 47.4 +/- 14.1 S.E. of mean pg/ml.). The endogenous velocity of renin production by foetal plasma was also greater than that of maternal plasma.2. Foetal plasma [Na(+)] (137 +/- 0.8 S.E. of mean m-equiv/l.), was lower than that in the ewe (142 +/- 1.5 m-equiv/l. S.E. of mean, P < 0.01).3. Foetal plasma renin in lambs of less than 120 days gestation was lower (9.2 +/- 2.7 S.E. of mean ng/ml.hr) than that in lambs of over 130 days gestation (12.6 +/- 2.6 ng/ml.hr S.E. of mean, P < 0.01). Foetal plasma [K(+)] (3.8 +/- 0.1 S.E. of mean m-equiv/l.) was also lower in lambs of less than 120 days gestation than in those over 130 days (4.1 +/- 0.1 S.E. of mean m-equiv/l., P < 0.001).4. When small volumes of blood (
TL;DR: The diastolic phase of pressure pulses recorded over a segment of the thoracic aorta several centimeters long centered about 4 cm cephalad to the dorsal insertion of the diaphragm could be closely approximated by a straight line on a semilogarithmic scale and correlated well with concomitant variations in peripheral vascular resistance.
Abstract: Large changes in stroke volume and peripheral vascular resistance were induced by varying the heart rate and by intra-aortically infusing acetylcholine or angiotensin II in six dogs with heart block and electromagnetic flowmeters chronically implanted around their ascending aortas. Changes in stroke volume, aortic and atrial pressures, and systemic resistance were monitored continuously for 3-6 hours under morphine-pentobarbital anesthesia. The characteristics of diastolic pressure decay at heart rates ranging from 60 beats/min to 200 beats/min and during transient periods of asystole were studied, especially with reference to the distortions caused by reflected pressure waves. The diastolic phase of pressure pulses recorded over a segment of the thoracic aorta several centimeters long centered about 4 cm cephalad to the dorsal insertion of the diaphragm could be closely approximated by a straight line on a semilogarithmic scale. Under the conditions of these experiments, changes in the slope of that line and of its reciprocal, the time constant, correlated well with concomitant variations in peripheral vascular resistance. This relationship appears to be of practical value for continuous monitoring of systemic resistance directly from the diastolic segments of pressure pulses recorded from the lower thoracic aorta.
TL;DR: The angiotensin I-converting enzyme was purified from homogenized hog kidney cortex and the ratios of rates of cleavage of dipeptides from the C-terminal end of three optically active substrates were similar for the hog plasma, kidney, and lung enzymes, but different from the human enzymes.
01 Jan 1974
TL;DR: The octapeptide, [5-isoleueine]-Angiotensin II which is specific to human, equine, rat and porcine species was synthesized by Bumpus et al. (1957) and Schwarz and Rittel (1956) and formed the basis for extensive studies of the biologic actions and structure-activity relationships of this hormone.
Abstract: The octapeptide, [5-isoleueine]-Angiotensin II which is specific to human, equine, rat and porcine species was synthesized by Bumpus et al. (1957) and Schwarz et al. (1957), while Rittel et al. (1957) synthesized [1-asparagine, 5-valine]-Ang. II, an analog of bovine Ang. II. These syntheses formed the basis for extensive studies of the biologic actions and structure-activity relationships of this hormone. The outcome of these efforts was the synthesis of over 90 analogs by early 1966. Bumpus and Smeby (1968) discussed the results in an earlier review and concluded that: a) the carboxyl terminal hexapeptide 3–8 sequence [Val-Tyr-Ile(Val)-His-Pro-Phe], composed of amino-acid residues with alternate aliphatic and aromatic side chains, carries the essential features of the hormone; b) all aromatic residues (4-tyrosine, 6-histidine, 8-phenylalanine) are essential for pressor activity while the aliphatic residues may be necessary either to stabilize a preferred conformation relative to the aromatic residues or to facilitate a favorable hydrophobic bonding on the receptor; and c) the carboxyl group at the C-terminus must be free.
TL;DR: Zona glomerulosa cells were isolated from the adult rat adrenal cortex and maintained in primary monolayer culture and the morphological and functional responses of the cells to different levels of potassium in the culture medium, and to serotonin, angiotensin II, ACTH and dibutyryl cyclic AMP were investigated.
Abstract: Zona glomerulosa cells were isolated from the adult rat adrenal cortex and maintained in primary monolayer culture. The morphological and functional responses of the cells to different levels of potassium in the culture medium, and to serotonin, angiotensin II, ACTH and dibutyryl cyclic AMP were investigated. Medium containing 11 mM K* stimulated aldosterone biosynthesis during the first week of culture to levels up to 100 times greater than those observed with 6 mM K*,althoug h in both cases aldosterone production eventually declined to undetectable levels. Serotonin at 0.1 and 1.0 mM initially stimulated aldosterone biosynthesis, but to lower levels than those obtained with 11 mM K*. Angiotensi n II at 10 and 100 μg/ml did not stimulate aldosterone biosynthesis by cultured rat zona glomerulosa cells. ACTH at 100 mU/ml, and dibutyryl cyclic AMP at 0.5 mM, initially stimulated aldosterone biosynthesis but later depressed i t to below levels seen in their absence. Thus none of these trophic stimuli were fo...
TL;DR: Observations support the hypothesis that increased cyclic AMP is associated with relaxation and increased Cyclic GMP with contraction of tracheal smooth muscle and additional studies are needed to examine this hypothesis more directly.